From the Guidelines
Amenorrhea is primarily caused by hormonal imbalances, particularly those affecting the hypothalamic-pituitary-ovarian axis, with polycystic ovary syndrome (PCOS) and functional hypothalamic amenorrhea (FHA) being two of the most common underlying conditions, as supported by recent studies 1. The causes of amenorrhea can be broadly categorized into primary and secondary amenorrhea. Primary amenorrhea occurs when menstruation never starts by age 15, while secondary amenorrhea is defined as the cessation of previously regular menstruation for a period of more than three months or previously irregular menstruation longer than 6 months 1. Some of the key medical conditions that can cause amenorrhea include:
- Polycystic ovary syndrome (PCOS), which is a form of hyperandrogenic chronic anovulation, affecting approximately 4–6% of women in the general population 1
- Functional hypothalamic amenorrhea (FHA), caused by chronic anovulation due to a functional reduction in the frequency of the pulsatile secretion of GnRH, affecting about 20–35% of cases of secondary amenorrhea 1
- Thyroid disorders, such as hypo- and hyperthyroidism
- Pituitary tumors
- Premature ovarian failure
- Structural problems like Asherman's syndrome or congenital absence of the uterus Certain medications, including some antipsychotics, antidepressants, chemotherapy drugs, and blood pressure medications, can also cause amenorrhea. It is essential for women experiencing amenorrhea to consult a healthcare provider for proper evaluation, as some causes require medical intervention while others may resolve with lifestyle modifications, and recent studies suggest that FHA is responsible for approximately one-third of the cases of secondary amenorrhea in women of reproductive age 1.
From the Research
Causes of Amenorrhea
The causes of amenorrhea can be categorized into several groups, including:
- Physiological causes, such as pregnancy and lactation 2
- Anatomical defects of the genital organs, including congenital and acquired anomalies of the uterus and vagina 2
- Endocrine dysfunctions, including:
- Hyperprolactinaemic amenorrhoea, often associated with a pituitary adenoma 2
- Hypogonadotrophic amenorrhoea, frequently associated with stress and nutritional deficiency 2
- Hypergonadotrophic amenorrhoea, resulting from ovarian failure 2
- Normogonadotrophic amenorrhoea, caused by disturbance in the pattern of pulsatile GnRH secretion, often associated with polycystic ovarian disease (PCO) 2
- Other causes, including:
- Chromosomal irregularities, such as Turner syndrome 3, 4
- Anatomic abnormalities, such as Müllerian agenesis 3
- Primary ovarian insufficiency 3, 4
- Hypothalamic amenorrhea, often associated with eating disorders and decreased bone density 3, 4, 5
- Thyroid disease, adrenal disease, and reproductive tract anomalies 5
Diagnostic Approach
The diagnostic approach to amenorrhea typically involves:
- A detailed history, including menstrual onset and patterns, eating and exercise habits, and presence of psychosocial stressors 4
- Physical examination, including anthropometric and pubertal development trends 4
- Laboratory assessment, including serum hormone levels, such as follicle-stimulating hormone, luteinizing hormone, prolactin, and thyroid-stimulating hormone 2, 3, 4
- Additional testing, such as karyotyping, serum androgen evaluation, and pelvic or brain imaging, as individualized 4
Treatment Approach
The treatment approach to amenorrhea depends on the underlying cause and may involve:
- Hormone replacement therapy, contraception, or infertility services for patients with primary ovarian insufficiency 4
- Treatment of underlying conditions, such as eating disorders, thyroid disease, or adrenal disease 3, 4, 5
- Preservation of bone density and prevention of fractures, as many causes of amenorrhea can result in decreased bone density 5